Suppressor T cells are a population of lymphocytes produced by the thymus and whose function is to suppress and therefore regulate, immune responses. They are particularly important in the induction of immunological tolerance and in the breakdown of normal tolerance to autoantigens, a situation that can lead to an "auto-immune" type of disease process. Suppressor T cells appear to play a role in auto-immune diseases involving the pituitary, ovary and throid gland. Although the pathogenesis of some cases of diabetes suggests that an auto-immune process might be involved, the role of suppressor T cells in pancreatic disease does not appear to have been investigated. The proposed research is designed to test the hypothesis that suppressor T cells have a role in the development and/or prevention of at least some cases of diabetes. The spontaneous development of abnormalities of pancreatic function, determined by glucose tolerance tests, plasma and pancreatic insulin levels, and morphology at the light and electron mircroscopic levels will be determined in rats which have either been neonatally thymectomized or perinatally thymectomized, thus reducing suppressor T cells numbers. In addition, similar studies will be performed on rats and mice that are recipients of graded numbers of spleen cells from syngeneic streptozotocin-induced diabetic donors or from spontaneously diabetic (db/db) mice. Cell transfer experiment will be performed employing graded numbers of spleen cells before and after culture under conditions designed to enhance either their cytotoxic or suppressor cell content. The latent period and severity of subsequent diabetes and/or its preventability with the various cell types will be assayed. As a correlate to the in vivo studies in vitro assessments of antigen-specific helper, cytotoxic and suppressor cells will be attempted employing cesium chloride coupled antigen - sheep red blood cell monolayers as tragets. Additionally the response of these cells in conventional mitogen assays will be determined.